This Program Announcement expires on March, 2004, unless reissued.
RESEARCH ON AUTISM AND AUTISM SPECTRUM DISORDERS
Release Date: February 13, 2001
PA NUMBER: PA-01-051 (see replacement PA-04-085)
National Institute on Deafness and Other Communication Disorders
National Institute of Mental Health
National Institute of Child Health and Human Development
National Institute of Neurological Disorders and Stroke
National Institute of Environmental Health Sciences
THIS PA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT
INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS
THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA.
PURPOSE
The purpose of this program announcement is to encourage grant
applications for the support of research designed to elucidate the
diagnosis, epidemiology, etiology, genetics, treatment, and optimal
means of service delivery in relation to Autistic Disorder ("autism")
and autism spectrum disorders (Rett's Disorder, Childhood
Disintegrative Disorder, Asperger's Disorder, Pervasive Developmental
Disorder-Not Otherwise Specified, or "Atypical Autism").
HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2010," a
PHS led national activity for setting priority areas. This Program
Announcement (PA), Research on Autism and Autism Spectrum Disorders, is
related to one or more of the priority areas. Potential applicants
may obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople/.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as principal investigators.
MECHANISM OF SUPPORT
This PA will use the National Institutes of Health (NIH) R01 award
mechanism. Responsibility for the planning, direction, and execution
of the proposed project will be solely that of the applicant. The
total project period for an application submitted in response to this
PA may not exceed five years.
Specific application instructions have been modified to reflect
"MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined
by the NIH. Complete and detailed instructions and information on
Modular Grant applications can be found at
http://grants.nih.gov/grants/funding/modular/modular.htm
RESEARCH OBJECTIVES
Although it has long been recognized that the pervasive developmental
disorders, including autism, are highly variable in their clinical
manifestations and likely the result of multiple etiologies, only
recently have efforts been directed toward a meaningful subtyping of
this group of disorders. Current classification systems (e.g., DSM-IV)
include five separate diagnoses under the pervasive developmental
disorders: Autistic Disorder, Rett's Disorder, Childhood Disintegrative
Disorder, Asperger's Disorder and Pervasive Developmental Disorder Not
Otherwise Specified (also called "Atypical Autism").
Autistic disorder, or "autism," is considered the most classic of the
pervasive developmental disorders in that it was the first of these
disorders to be recognized as a distinct disorder. These disorders
share a cluster of impairments in reciprocal social interaction and
communication and/or the presence of stereotyped behavior, interests
and activities. These complex disorders are usually of lifelong
duration and affect multiple aspects of development, learning, and
adaptation in the community, and thus represent a pressing public
health need. The etiologies of these disorders are poorly understood,
but are thought to include genetic, metabolic, immunologic and
infectious or other environmental influences.
Etiology research involving these requires well integrated, multi-
disciplinary, methodologically-rigorous scientific approaches and
access to a sufficient number of well-characterized patients with these
disorders. Basic research into the pathophysiology of autism and
autism spectrum disorders, including research on brain mechanisms and
genetics, is of special interest. Also of interest are clinical and
applied investigations that may lead to the development of diagnostic
research instruments, treatments, and intervention strategies.
Specific areas of interest thus include epidemiology, early
identification and diagnosis, genetic studies, brain mechanisms,
communication skills, cognitive neuroscience, psychosocial (behavioral)
interventions, pharmacological and other biological interventions, and
services.
Areas of interest include, but need not be limited to, the following:
o Epidemiology: Development of new screening tools for use in a
variety of settings; research on the expression of the full range of
autism spectrum disorders; studies on their developmental course;
studies that characterize the range of expression within families;
research on co-occurring features; and studies to determine risk
factors in the etiology of autism, including environmental exposures
during pregnancy and early childhood.
o Early Identification and Diagnosis: Key diagnostic features
associated with various stages of development; assessment of comorbid
features including hyperactivity, attentional dysfunctions, epilepsy,
and obsessive and compulsive symptoms; assessment and further
differentiation of subtypes of autistic spectrum disorders including
Autistic Disorder, Asperger's Disorder, Rett's Disorder, and Childhood
Disintegrative Disorder; and, developmental factors relevant to
reliable and valid diagnosis.
o Genetic Studies: Large-scale linkage studies of affected relative
pairs or extended pedigrees to identify chromosomal regions harboring
disease susceptibility genes; family-based association analysis and
other linkage disequilibrium approaches that aim to identify a
specific susceptibility gene; high-resolution mapping and positional
cloning studies; resolution of locus heterogeneity; analysis of the
interaction of autism susceptibility gene(s) with environmental
exposures and/or genes responsive to environmental insult, testing for
potential candidate genes.
o Brain Mechanisms: Studies of brain mechanisms underlying the
development, regulation, and modulation of behaviors characterizing
autism and autism spectrum disorders, particularly those mechanisms
involving communication and social interaction; studies of brain
mechanisms and biological factors underlying autistic regression, or
the loss of previously acquired skills; studies of brain mechanisms
involved in the development of abnormal electroencephalograms and
epilepsy and studies to clarify the subtypes of seizures and seizure
disorders in autism; studies to define the neurobiological basis of
neurological abnormalities and neuropsychiatric symptoms, including
motor stereotypies, gait abnormalities, akinesias, dyskinesias,
obsessive/compulsive traits, and the exacerbation of these symptoms,
including the role of neuroimmune/autoimmune factors; studies that seek
to define basic processing deficits using neuropsychological and
cognitive neuroscience techniques; studies to develop animal models of
brain dysfunction in autism and autism spectrum disorders, based on
either genetic or environmental factors or their interaction.
o Communication Skills: Longitudinal, developmental studies of
behaviors that are precursors to later communication (e.g., imitation,
joint attention, early vocalization) and their emergence in children
with autism and autistic spectrum disorders; sensory, motor and social-
cognitive impairments that impact upon interaction and communication;
predictors of loss of or regression in expressive language abilities;
the nature of severe spoken language deficits when other areas of
function, such as written language skills, are relatively preserved;
interventions designed to remediate communication and related deficits.
o Cognitive Science: Developmental studies of relevant behaviors
during infancy including attention to social and nonsocial stimuli,
affective behavior, gaze, vocalization, imitation, initiative,
reciprocity, attachment, play, compliance, and self- recognition and
their emergence in children with autism and autistic spectrum
disorders; research on the delays and deviations in social behavior and
cognition during preschool and middle school, including empathy,
receptive social cognitive deficits (i.e., difficulties understanding
others), and expressive difficulties; studies leading to more
sophisticated tests of higher cognitive functioning, especially in
social, communicative, reasoning, and problem-solving areas, as well as
tests of basic attentional, emotional and cognitive deficits that may
underlie these deficits or be precursors to them; studies of theory of
mind, of unconventional verbal behaviors, and of the sensory-motor
factors involved in relevant social cognition; and the development,
validation and refinement of interventions designed to address deficits
in complex social and cognitive abilities or their developmental
precursors.
o Psychosocial Interventions: Studies developing new treatments
(e.g., behavioral, cognitive-behavioral) and studies validating,
refining and comparing approaches to the treatment of autism and autism
spectrum disorders, as well as studies that analyze and define the
critical features of effective intervention; studies that relate
characteristics of individuals (or diagnostic subtypes) to treatment
outcomes; research on relevant contextual factors including physical
environments, parent-child and sibling-child relationship factors, and
peer-child interactions; studies addressing generalization or the
transfer of learning from one setting to another.
o Pharmacological/Biological Intervention: Studies aimed at
developing and testing the efficacy and safety of pharmacological
agents that specifically target the core features of autism and
autistic spectrum disorders; studies of the efficacy and safety of
pharmacological and combined treatments for the most common and
impairing psychopathology associated with autism (e.g., hyperactivity,
impulsivity, aggression, self-injury, and obsessive-compulsive
symptoms); new approaches to treatment that build on advances in
neuroscience, genetics, immunology, and other neurobiologic fields;
focused interventions that test specific theories or hypotheses
regarding possible neuropathogenesis; studies that address the benefits
of combined drug and psychosocial interventions.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups
and their sub-populations must be included in all NIH-supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification are provided
indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43).
All investigators proposing research involving human subjects should
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities
as Subjects in Clinical Research," published in the NIH Guide for
Grants and Contracts on August 2, 2000
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a
complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm.
The revisions relate to NIH defined Phase III clinical trials and
require: a) all applications or proposals and/or protocols to provide a
description of plans to conduct analyses, as appropriate, to address
differences by sex/gender and/or racial/ethnic groups, including
subgroups if applicable; and b) all investigators to report accrual,
and to conduct and report analyses, as appropriate, by sex/gender
and/or racial/ethnic group differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS
It is the policy of NIH that children (i.e., individuals under the age
of 21) must be included in all human subjects research, conducted or
supported by the NIH, unless there are scientific and ethical reasons
not to include them. This policy applies to all initial (Type 1)
applications submitted for receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should
read the "NIH Policy and Guidelines on the Inclusion of Children as
Participants in Research Involving Human Subjects" that was published
in the NIH Guide for Grants and Contracts, March 6, 1998, and is
available at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.
Investigators also may obtain copies of these policies from the program
staff listed under INQUIRIES. Program staff may also provide
additional relevant information concerning the policy.
URLS IN NIH GRANT APPLICATIONS OR APPENDICES
All applications and proposals for NIH funding must be self-contained
within specified page limitations. Unless otherwise specified in an
NIH solicitation, internet addresses (URLs) should not be used to
provide information necessary to the review because reviewers are under
no obligation to view the Internet sites. Reviewers are cautioned that
their anonymity may be compromised when they directly access an
Internet site.
APPLICATION PROCEDURES
Applications are to be submitted on the grant application form PHS 398
(rev. 4/98) and will be accepted at the standard application deadlines
as indicated in the application kit. Application kits are available at
most institutional offices of sponsored research and may be obtained
from the Division of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone 301/435-0714, email:
GrantsInfo@nih.gov.
Applicants planning to submit an investigator-initiated new (type 1),
competing continuation (type 2), competing supplement, or any
amended/revised version of the preceding grant application types
requesting $500,000 or more in direct costs for any year are advised
that he or she must contact the Institute or Center (IC) program staff
before submitting the application, i.e, as plans for the study are
being developed. Furthermore, the application must obtain agreement
from the IC staff that the IC will accept the application for
consideration for award. Finally, the applicant must identify, in a
cover letter sent with the application, the staff member and Institute
or Center who agreed to accept assignment of the application.
This policy requires an applicant to obtain agreement for acceptance of
both any such application and any such subsequent amendment. Refer to
the NIH Guide for Grants and Contracts, March 20, 1998 at
http://grants.nih.gov/grants/guide/notice-files/not98-030.html.
The modular grant concept establishes specific modules in which direct
costs may be requested as well as a maximum level for requested
budgets. Only limited budgetary information is required under this
approach. The just-in-time concept allows applicants to submit certain
information only when there is a possibility for an award. It is
anticipated that these changes will reduce the administrative burden
for the applicants, reviewers and Institute staff. The research grant
application form PHS 398 (rev. 4/98) is to be used in applying for
these grants, with the modifications noted below.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS
The title and number of the program announcement must be typed on line
2 of the face page of the application form and the YES box must be
marked.
BUDGET INSTRUCTIONS
Modular Grant applications will request direct costs in $25,000
modules, up to a total direct cost request of $250,000 per year.
(Applications that request more than $250,000 direct costs in any year
must follow the traditional PHS 398 application instructions.) The
total direct costs must be requested in accordance with the program
guidelines and the modifications made to the standard PHS 398
application instructions described below:
PHS 398.
o FACE PAGE: Items 7a and 7b should be completed, indicating Direct
Costs (in $25,000 increments up to a maximum of $250,000) and Total
Costs [Modular Total Direct plus Facilities and Administrative (F&A)
costs] for the initial budget period Items 8a and 8b should be
completed indicating the Direct and Total Costs for the entire proposed
period of support.
o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form
Page 4 of the PHS 398. It is not required and will not be accepted with
the application.
o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete
the categorical budget table on Form Page 5 of the PHS 398. It is not
required and will not be accepted with the application.
o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget
Narrative page. (See http://grants.nih.gov/grants/funding/modular/modular.htm
for sample pages.) At the top of the page, enter the total direct costs
requested for each year. This is not a Form page.
o Under Personnel, list all project personnel, including their names,
percent of effort, and roles on the project. No individual salary
information should be provided. However, the applicant should use the
NIH appropriation language salary cap and the NIH policy for graduate
student compensation in developing the budget request.
For Consortium/Contractual costs, provide an estimate of total costs
(direct plus facilities and administrative) for each year, each rounded
to the nearest $1,000. List the individuals/organizations with whom
consortium or contractual arrangements have been made, the percent
effort of all personnel, and the role on the project. Indicate whether
the collaborating institution is foreign or domestic. The total cost
for a consortium/contractual arrangement is included in the overall
requested modular direct cost amount. Include the Letter of Intent to
establish a consortium.
Provide an additional narrative budget justification for any variation
in the number of modules requested.
o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information
used by reviewers in the assessment of each individual's qualifications
for a specific role in the proposed project, as well as to evaluate the
overall qualifications of the research team. A biographical sketch is
required for all key personnel, following the instructions below. No
more than three pages may be used for each person. A sample
biographical sketch may be viewed at:
http://grants.nih.gov/grants/funding/modular/modular.htm
- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;
o CHECKLIST - This page should be completed and submitted with the
application. If the F&A rate agreement has been established, indicate
the type of agreement and the date. All appropriate exclusions must be
applied in the calculation of the F&A costs for the initial budget
period and all future budget years.
o The applicant should provide the name and phone number of the
individual to contact concerning fiscal and administrative issues if
additional information is necessary following the initial review.
Submit a signed, typewritten original of the application, including the
Checklist, and five signed photocopies in one package to:
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
REVIEW CONSIDERATIONS
Applications will be assigned on the basis of established PHS referral
guidelines. Applications will be evaluated for scientific and
technical merit by an appropriate scientific review group convened in
accordance with the standard NIH peer review procedures. As part of
the initial merit review, all applications will receive a written
critique and undergo a process in which only those applications deemed
to have the highest scientific merit, generally the top half of
applications under review, will be discussed, assigned a priority
score, and receive a second level review by the appropriate national
advisory council or board.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
In the written comments reviewers will be asked to discuss the
following aspects of the application in order to judge the likelihood
that the proposed research will have a substantial impact on the
pursuit of these goals. Each of these criteria will be addressed and
considered in assigning the overall score, weighting them as
appropriate for each application. Note that the application does not
need to be strong in all categories to be judged likely to have major
scientific impact and thus deserve a high priority score. For example,
an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.
(1) Significance: Does this study address an important problem? If
the aims of the application are achieved, how will scientific knowledge
be advanced? What will be the effect of these studies on the concepts
or methods that drive this field?
(2) Approach: Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to the
aims of the project? Does the applicant acknowledge potential problem
areas and consider alternative tactics?
(3) Innovation: Does the project employ novel concepts, approaches or
method? Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies?
(4) Investigator: Is the investigator appropriately trained and well
suited to carry out this work? Is the work proposed appropriate to the
experience level of the principal investigator and other researchers
(if any)?
(5) Environment: Does the scientific environment in which the work
will be done contribute to the probability of success? Do the proposed
experiments take advantage of unique features of the scientific
environment or employ useful collaborative arrangements? Is there
evidence of institutional support?
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will
also be evaluated.
o The reasonableness of the proposed budget and duration in relation
to the proposed research
o The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the
project proposed in the application.
AWARD CRITERIA
Applications will compete for available funds with all other
recommended applications. The following will be considered in making
funding decisions: Quality of the proposed project as determined by
peer review, availability of funds, and program priority.
INQUIRIES
Inquiries are encouraged. Questions and discussion of programmatic
issues from potential applicants may be addressed to:
Judith Cooper, Ph.D.
Division of Extramural Research
National Institute on Deafness and Other Communication Disorders
Executive Plaza South, Room 400C-11 - MSC 7180
Bethesda, MD 20892-7180
Telephone: (301) 496-5061
FAX: (301) 402-6251
Email: Judith_Cooper@nih.gov
Steve Foote, Ph.D.
National Institute of Mental Health
NSC, 6100 Executive Boulevard, Room 7204
Bethesda, MD 20857-MSC-9645
Telephone: (301) 443-3563
FAX: (301) 443-1731
Email: Sfoote@mail.nih.gov
Marie Bristol-Power, Ph.D.
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B09E, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-1383
FAX: (301) 496-3791
Email: Bristolm@exchange.nih.gov
Deborah Hirtz, M.D.
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard
Bethesda, MD 20892
Telephone: (301) 496-5821
FAX: (301) 480-1080
Email: dh83f@nih.gov
Cindy P. Lawler, Ph.D.
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-23
Research Triangle Park, NC 27709
Telephone: (919) 316-4671
FAX: (919) 541-5064
Email: lawler@niehs.nih.gov
Direct inquiries regarding fiscal matters to:
Diana Trunnell
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-2805
FAX: (301) 443-6885
Email: Diana_Trunnell@nih.gov
Mary E. Daley
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A07 - MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-1305
FAX: (301) 402-0915
Email: md74u@nih.gov
Sara Stone
Chief, Grants Management Branch
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, EPS-400-B MSC-7180
Bethesda, MD 20892-7180
Telephone: (301) 402-0909
FAX: (301) 402-1758
Email: Sherry_Dabney@nih.gov
Gladys Melendez-Bohler
Grants Management Office
National Institute of Neurological Disorders and Stroke
NSC, Room 3262
Bethesda, MD 20892
Telephone: (301) 496-3929
FAX: (301) 402-0219
Email: bohlerg@ninds.nih.gov
Laura Williams-Boyd
Grants Management Branch
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-23
Research Triangle Park, NC 27709
Telephone: (919) 541-7629
FAX: (919) 541-2860
Email: willia27@niehs.nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
No. 93.173. Awards are made under authorization of sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284)
and administered under NIH grants policies and Federal Regulations 42
CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products. In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, and
portion of a facility) in which regular or routine education, library,
day care, health care or early childhood development services are
provided to children. This is consistent with the PHS mission to
protect and advance the physical and mental health of the American
people.